Anlotinib suppressed tumor cell proliferation and migration in hypopharyngeal carcinoma.

OBJECTIVE: The purpose of this study is to study the in-vitro effects of multitarget inhibitor anlotinib on hypopharyngeal cancer cell proliferation and cell migration, and the underlying mechanism, which will provide new drug choices for hypopharyngeal cancer treatment. METHODS: The Hypopharyngeal cancer Fadu cells were treated with anlotinib at a concentration of 0, 5, and 10 µmoL/L, respectively. Cell counting kit-8 and the colony-forming assay were used to detect the inhibition of cell proliferation. Wound-healing assay and transwell assay were used to detect the migration and invasion ability of cells. Flow cytometry was used to detect the effects of anlotinib on cell cycle and apoptosis. RT-qPCR and Western blot were used to measure gene expression levels. RESULTS: CCK-8 and colony-forming assay showed that anlotinib could significantly inhibit cell proliferative activity. Wound-healing assay and transwell assay showed that anlotinib could inhibit cell migration and scratch. These results showed that anlotinib has obvious antitumor activity. Flow cell cycle experiment showed that anlotinib could promote Fadu cell apoptosis and block the G2/M phase for inhibiting cell proliferation. In addition, anlotinib decreased the expression of HIF-1α. CONCLUSIONS: Anlotinib has an excellent suppressing effect on the proliferation, migration, and invasion of hypopharyngeal cancer Fadu cells in-vitro. Moreover, it can play an anti-tumor role through blocking cell cycle G2/M and promoting apoptosis, which may be related to the decrease of HIF-1a expression. Our study would provide a potential treatment method for patients with hypopharyngeal cancer. LEVEL OF EVIDENCE: Level 3.

The role and clinical significance of microRNA-29a-3p in the development of hypopharyngeal carcinoma.

OBJECTIVE: MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. METHODS: 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. RESULTS: Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p < 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p < 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. CONCLUSIONS: The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using "Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence".

Linfangioma hipofaríngeo en adulto: presentación de un caso clínico / Hypopharyngeal lymphangioma in adults: Presentation of a case report

Los linfangiomas son malformaciones linfáticas benignas infrecuentes; se manifiestan principalmente en la infancia. Pueden desarrollarse en cualquier zona del cuerpo, más frecuentemente cabeza y cuello, siendo su compromiso faríngeo extremadamente poco común. Dada su clínica inespecífica se requiere un análisis anatomopatológico preciso para concretar un correcto diagnóstico. Presentamos el caso de una mujer de 40 años con historia de disfagia y odinofagia de un año de evolución cuyo estudio imagenológico y con nasofibroscopía evidenció un tumor redondeado alojado en seno piriforme derecho, la biopsia excisional confirmó el diagnóstico de linfangioma. Se debe considerar el diagnóstico de linfangioma dentro de los diagnósticos diferenciales de tumores en faringe y concientizar su presencia en pacientes adulto, para ofrecer el manejo óptimo basado, ya sea en escisión quirúrgica completa, para evitar la recurrencia asociado, o al uso de sustancias esclerosantes.

Lymphangiomas are infrequent benign lymphatic malformations, with clinical manifestations mainly at birth or in childhood. They can develop in any area of the body, most frequently the head and neck, and their pharyngeal involvement is extremely rare. Given its nonspecific symptoms, it requires a precise pathological analysis to make a correct diagnosis. We present the case of a 40-year-old woman with a 1-year history of dysphagia and odynophagia whose imaging study and nasofibroscopy revealed a rounded tumor lodged in the right pyriform sinus. The excisional biopsy confirmed the diagnosis of lymphangioma. The diagnosis of lymphangioma should be considered within the differentials of tumors in the pharynx and awareness of its presence in adults to offer optimal management based on complete surgical excision to avoid recurrence or management with use of sclerosing substances.

Oncological outcomes from surgical vs. non-surgical treatments for advanced hypopharyngeal squamous cell carcinoma: a surveillance, epidemiology, and end results-based study.

OBJECTIVE: Patients with advanced hypopharyngeal squamous cell carcinomas (HSCCs) have poor prognoses. The use of surgical or non-surgical treatments for these patients remains a topic of debate. This study compared survival following surgical and non-surgical treatments of patients with advanced HSCC based on the Surveillance, Epidemiology and End Results (SEER) database. METHODS: Patients diagnosed with hypopharyngeal cancer from 2004 to 2018 were identified from the SEER database. Patients were divided into non-surgical group and surgical group, and patients in the surgical group were further divided into three groups: surgery-only, surgery with adjuvant radiation therapy and surgery with adjuvant chemoradiation therapy. The primary endpoint was overall survival (OS), and the secondary outcome was cancer-specific survival (CSS). Outcomes were analyzed using Kaplan-Meier analysis. A multivariate Cox regression analysis was also used to identify independent prognostic factors. RESULTS: The records of 1568 eligible patients with stage III or IV HSCC were examined. Receipt of surgery was associated with a longer OS [hazard ratio (HR) = 0.47, 95% confidence interval (CI): 0.4-0.56] and a longer CSS (HR = 0.47, 95% CI: 0.38-0.57) after adjusting for age, sex, race, tumor site, tumor size, tumor grade, TNM stage, AJCC stage, number of carcinomas, prior cancer, receipt of radiotherapy, and receipt of chemotherapy. The results for OS were similar in an exploratory analysis of different patient subgroups. CONCLUSION: Among patients with advanced HSCC in the SEER database, treatment with surgery was associated with longer OS and CSS than treatment with a non-surgical modality.

Carcinoma of the posterior wall of the hypopharynx: surgical treatment with larynx preservation / Carcinoma da parede posterior da hipofaringe: tratamento cirúrgico com preservação da laringe

Abstract Introduction: Posterior pharyngeal wall is the most rare subsite for hypopharyngeal carcinomas. Because of its rarity, there are few studies published in the literature specifically concerning posterior pharyngeal wall carcinoma. Objectives: To report our functional results in patients with the carcinoma of the posterior wall of the hypopharynx after surgical treatment by resection via a lateral or infrahyoid pharyngotomy approach, with the preservation of the larynx and reconstruction with a radial forearm free flap. Methods: The study included 10 patients who underwent surgery for a carcinoma of the posterior wall of the hypopharynx over a 6 year period. The associated postoperative morbidity was investigated and functional results were analyzed. Results: Nine patients had T3 lesions and one patient had a T2 lesion. The preferred approach to access the hypopharynx was a lateral pharyngotomy in 5 patients and lateral pharyngotomy combined with infrahyoid pharyngotomy in 5 patients with superior extension to oropharynx. The pharyngeal defects were reconstructed successfully with radial forearm free flaps. Four patients received adjuvant radiotherapy only, and 4 patients with N2b and N2c neck diseases received adjuvant chemoradiotherapy. The mean duration of hospitalization was 15.6 days (range, 10-21 days). All patients achieved oral intake in a median time of 74 days (range, 15-180). Decannulation was achieved in all patients and the median time fordecannulation was 90 (range, 21-300 days). The mean followup duration was 38.3 months (range, 10-71 months) and 8 patients survived. One patient died due to regional recurrence in the retropharyngeal lymph nodes and 1 patient died due to systemic metastasis. Conclusion: Primary surgery is still a very effective treatment modality for the carcinoma of the posterior wall of the hypopharynx and does not permanently compromise the swallowing and laryngeal functions if pharyngeal reconstruction is performed with a free flap.

Resumo Introdução: A parede posterior da faringe é o subsítio mais raro para carcinomas hipofaríngeos. Devido à sua raridade, há poucos estudos publicados na literatura especificamente sobre o carcinoma da parede posterior da faringe. Objetivo: Relatar nossos resultados funcionais em pacientes com carcinoma da parede posterior da hipofaringe após tratamento cirúrgico por ressecção via faringotomia lateral ou infra-hióidea, com preservação da laringe e reconstrução com retalho livre radial do antebraço. Método: O estudo incluiu 10 pacientes submetidos à cirurgia para carcinoma da parede posterior da hipofaringe por 6 anos. A morbidade pós-operatória associada foi investigada e os resultados funcionais foram analisados. Resultados: Nove pacientes apresentaram lesões T3 e um paciente apresentou lesão T2. Avia preferida para acessar a hipofaringe foi a faringotomia lateral em 5 pacientes e a faringotomia lateral combinada com a faringotomia infra-hióidea em 5 pacientes com extensão superior até a orofaringe. Os defeitos faríngeos foram reconstruídos com sucesso com retalhos livres radiais do antebraço. Quatro pacientes receberam apenas radioterapia adjuvante e 4 pacientes com doença cervical N2b e N2c receberam quimiorradioterapia adjuvante. A duração média da hospitalização foi de 15,6 dias (variação de 10 a 21 dias). Todos os pacientes retornaram à ingestão oral em um tempo médio de 74 dias (variação de 15 a 180). A decanulação foi possível para todos os pacientes e o tempo médio foi de 90 dias (variação de 21 a 300 dias). A duração média do seguimento foi de 38,3 meses (10 a 71 meses) e 8 pacientes sobreviveram. Um paciente foi a óbito devido a recorrência regional nos linfonodos retrofaríngeos e outro devido a metástase sistêmica. Conclusão: A cirurgia primária ainda é uma modalidade de tratamento muito eficaz para o carcinoma da parede posterior da hipofaringe e não compromete de forma permanente as funções de deglutição e da laringe se a reconstrução faríngea for feita com retalho livre.

Carcinoma of the posterior wall of the hypopharynx: surgical treatment with larynx preservation.

INTRODUCTION: Posterior pharyngeal wall is the most rare subsite for hypopharyngeal carcinomas. Because of its rarity, there are few studies published in the literature specifically concerning posterior pharyngeal wall carcinoma. OBJECTIVES: To report our functional results in patients with the carcinoma of the posterior wall of the hypopharynx after surgical treatment by resection via a lateral or infrahyoid pharyngotomy approach, with the preservation of the larynx and reconstruction with a radial forearm free flap. METHODS: The study included 10 patients who underwent surgery for a carcinoma of the posterior wall of the hypopharynx over a 6 year period. The associated postoperative morbidity was investigated and functional results were analyzed. RESULTS: Nine patients had T3 lesions and one patient had a T2 lesion. The preferred approach to access the hypopharynx was a lateral pharyngotomy in 5 patients and lateral pharyngotomy combined with infrahyoid pharyngotomy in 5 patients with superior extension to oropharynx. The pharyngeal defects were reconstructed successfully with radial forearm free flaps. Four patients received adjuvant radiotherapy only, and 4 patients with N2b and N2c neck diseases received adjuvant chemoradiotherapy. The mean duration of hospitalization was 15.6 days (range, 10-21 days). All patients achieved oral intake in a median time of 74 days (range, 15-180). Decannulation was achieved in all patients and the median time for decannulation was 90 (range, 21-300 days). The mean followup duration was 38.3 months (range, 10-71 months) and 8 patients survived. One patient died due to regional recurrence in the retropharyngeal lymph nodes and 1 patient died due to systemic metastasis. CONCLUSION: Primary surgery is still a very effective treatment modality for the carcinoma of the posterior wall of the hypopharynx and does not permanently compromise the swallowing and laryngeal functions if pharyngeal reconstruction is performed with a free flap.

The role of MMP-2 and MMP-9 in the metastasis and development of hypopharyngeal carcinoma.

INTRODUCTION: The role of matrix metalloproteinase-2 and 9 in the metastasis and development of hypopharyngeal carcinoma has not been clarified. OBJECTIVES: To observe the relationship between matrix metalloproteinase-2, matrix metalloproteinase-9 and the metastasis, development of hypopharyngeal carcinoma. METHODS: This study included 42 hypopharyngeal cancer patients. The mRNA and protein expression levels of matrix metalloproteinase-2 and 9 in hypopharyngeal carcinoma and paracancerous tissues were detected by reverse transcription-polymerase chain reaction and Western blot. RESULTS: Reverse transcription-polymerase chain reaction detection showed that the mRNA of matrix metalloproteinase-2 and 9 was expressed in both cancer and pericarcinoma tissues, but was almost not expressed in polypoid control tissues. The expression intensity in the cancer tissue was significantly higher than that in the pericarcinoma tissue (matrix metalloproteinase-2: t ＝ 2.529, p = 0.015; matrix metalloproteinase-9: t ＝ 4.781, p ＜ 0.001). The mRNA expression in the cancer tissue was enhanced with the increase of the tumor clinical stage (matrix metalloproteinase-2: F = 4.003, p = 0.026; matrix metalloproteinase-9: F = 5.501, p = 0.008). Its expression intensity was associated with the metastasis of lymph nodes (N staging) and increased with the degree of lymphatic metastasis (matrix metalloproteinases-2: F = 8.965, p = 0.005; matrix metalloproteinase-9: F = 5.420, p = 0.025). There was no significant change in T staging of tumor. With the increase of tumor pathological stage, the mRNA expression of matrix metalloproteinase-2 and 9 was strengthened (matrix metalloproteinase-2: F = 3.884, p = 0.029; matrix metalloproteinase-9: F = 3.783, p = 0.032). The protein expression level of matrix metalloproteinase-2 and 9 was the same as that of mRNA. CONCLUSION: The expression of matrix metalloproteinase-2 and 9 in hypopharyngeal carcinoma was significantly higher than that in pericarcinoma tissue, and it was enhanced with the increase of clinical stage. The expression level was related to lymph node metastasis and tumor pathological stage. Thus, matrix metalloproteinase-2 and 9 may be involved in the occurrence, development, invasion and metastasis of hypopharyngeal carcinoma through a variety of mechanisms.

Long-term outcomes of induction chemotherapy followed by chemoradiotherapy vs chemoradiotherapy alone as treatment of unresectable head and neck cancer: follow-up of the Spanish Head and Neck Cancer Group (TTCC) 2503 Trial.

BACKGROUND: Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. MATERIALS AND METHODS: Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. RESULTS: In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8-34.4), 26.2 (95% CI, 18.2-36.6) and 25.4 months (95% CI, 17.4-36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rank p = 0.51). In the per-protocol population (n = 355), patients with larynx-hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. CONCLUSION: After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx-hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team. ClinicalTrials.gov identifier NCT00261703.

Head and Neck Microvascular Reconstruction in Puerto Rico: Developing a Two-team approach to Microvascular Reconstructive Surgery.

Hypopharyngeal carcinoma as a subsite of head and neck cancer, carries with it the lowest 5-year relative survival rate. Treatment of hypopharyngeal cancer relies on single therapy or multimodality treatment: surgery, radiation and/or chemotherapy. When surgical intervention is chosen, the type of operation depends on the extent of the lesion and the regions involved and will often require some form of reconstruction. We present the case of a 69-year-old male patient with T4aN3M0 hypopharyngeal carcinoma treated in Puerto Rico utilizing a two-team approach for removal of the primary tumor as well as harvesting of the free-flap for reconstruction. This approach allows for decreased operative time by having two surgical teams operating at the same time. The benefits of free flap reconstruction include: larger resection margins, better functional outcomes in terms of swallowing, and decreased post-operative morbidity in irradiated patients.

The importance of adjuvant treatment and primary anatomical site in head and neck basaloid squamous cell carcinoma survival: an analysis of the National Cancer Database.

PURPOSE: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that accounts for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within BSCC subtype and its impact on survival. METHODS: A cohort of 1999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy. RESULTS: The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The presence of metastasis increased the risk of mortality (HR = 2.14; 95% CI 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR = 2.45; 95% CI 1.83-3.29), hypopharynx (HR = 2.58; 95% CI:1.64-4.05), and larynx (HR = 2.89; 95% CI:2.25-3.73). Adjuvant chemoradiation (HR = 0.36; 95% CI 0.23-0.58) and adjuvant radiation (HR = 0.38; 95% CI 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy. Patients with microscopic margins had better survival outcomes when compared to no surgery (HR = 0.38, 98% Cl 0.23-0.64) while there were no better survival outcomes of patients with macroscopic margins compared to no surgery. CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, and microscopic margins were associated with greater survival.

Treatment for postchemoradiotherapy hypopharyngeal stenosis: Pharyngoesophageal bypass using an anterolateral thigh flap-A case report.

Radiation-induced pharyngoesophageal stenosis is a frequent and unwanted consequence of nonsurgical treatment of hypopharyngeal carcinomas. Current treatment mainly includes endoscopic dilatations, but a poor response to this modality and/or a severe stenosis may lead to a radical resection (pharyngolaryngectomy) and reconstruction with tubed flaps, which allow oral feeding but fail to preserve speech. In this report, we present a case of radiation-induced hypopharyngeal stenosis treated with a pharyngoesophageal bypass using an anterolateral thigh (ALT) flap with the intention of preserving the larynx. We describe the case of a 59-year-old male with severe pharyngoesophageal stenosis after chemoradiotherapy due to a squamous cell carcinoma, where conventional dilatation treatment failed to restore pharyngoesophageal passage of solids or liquids. Since the patient rejected a pharyngolaryngectomy due the loss of speech entailed, a pharyngoesophageal bypass was performed using an ALT flap. The flap measured 13 × 20 cm, which ensured a 4-cm-diameter tube and enough length to communicate the lateral pharyngeal wall with the cervical esophagus. Endoscopy did not reveal flap failure, and during the immediate postoperative period, the patient had a small cervical leak detected only by imaging that did not affect the skin and resolved with antibiotic treatment. The patient also required a tracheostomy on day 4 and initially had no passage of saliva through the bypass; we attributed this to edema that resolved spontaneously after 1 month with complete liquid and solid passage and laryngeal competence that led to tracheal decannulation. Good functional results were achieved both for speech and swallowing at 5-year follow-up. We believe that this procedure may be considered before performing a pharyngolaryngectomy for the treatment of a persistent benign stenosis in patients with a functional larynx.

Treatment Options for Hypopharyngeal Cancer in Developing Countries in Africa/South America/Asia.

Most cancers occur in developing countries, and therefore, a discussion about cancer care would be incomplete without providing a developing world perspective. This chapter focuses on challenges and practices relating to hypopharyngeal cancer in limited-resource public healthcare systems in developing countries and specifically in Sub-Saharan Africa, India and South America and by extension, most patients in the developing world. Management of hypopharyngeal cancer must be adapted to the availability of specialised diagnostic and therapeutic services, radiotherapy and surgical expertise, and tailored to patient factors such as reliability of follow-up and social support. A particular challenge for physicians is to decide who can be denied the opportunity to be cured when the burden of cancer cases exceeds available resources. Public education campaigns about reducing risk factors for hypopharyngeal cancer are an important aspect of reducing the burden of cancer.

Expanding the applications of the combined transverse upper gracilis and profunda artery perforator (TUGPAP) flap for extensive defects.

BACKGROUND: The medial thigh is a well-hidden area. The two most common flaps from this area are the transverse upper gracilis (TUG) and profunda artery perforator (PAP) flaps. Herein, we explored the applications of combined TUGPAP flap to reconstruct large and complex defects in different regions. METHODS: Between November 2015 and May 2017, 28 patients who underwent reconstruction and extensive soft tissue coverage with the TUGPAP flap for the breasts, head and neck, and pelvi-perineal regions were included. The defects size ranged from 22 to 29 × 6-8 cm. All flaps were based on the two pedicles: the medial circumflex femoral artery for TUG flap and the profunda artery perforator for PAP flap. They were each anastomosed to a set of recipient vessels. A "Y"-shaped interposition vein graft (YVG) was used if only one recipient artery was available. RESULTS: The harvested skin paddle had dimensions ranged from 20 to 30 × 6-9 cm and all flaps survived completely. Postoperative complications included one case each of donor and recipient site seroma, and one case of wound dehiscence. They were all successfully managed conservatively. During an average follow-up period of 12.7 months, one patient reported permanent paresthesia in the donor site and another developed hypertrophic scar. All patients were able to resume daily activity without major concerns. CONCLUSION: The combined TUGPAP flap is a safe, effective, and a good alternative to the common workhorse flaps as it offers the potential for a large skin paddle and decent soft tissue volume with low donor site morbidity in a well-concealed area.

Surgically-Treated Locoregionally Advanced Hypopharyngeal Cancer: Outcomes

Abstract Introduction Hypopharyngeal tumors are head and neck malignancies associated with a great mortality rate, and the treatment of advanced lesions constitutes a challenging problem. Pharyngolaryngectomy continues to be the gold standard treatment modality for locally-advanced diseases, and it is currently used as the primary treatment or in cases of relapse after an organ preservation strategy. Objective This study aims to compare the survival rates of patients with advanced hypopharyngeal tumors treated with pharyngolaryngectomy as a primary or salvage option, and identify possible prognostic factors. Methods All patients with advanced hypopharyngeal squamous cell carcinomas who performed pharyngolaryngectomy between 2007 and 2014 were reviewed retrospectively. Results A total of 87 patients fulfilled the aforementioned criteria, and the sample had a mean age of 57.2 years and a male predominance of 43:1. The tumors were located in the pyriform sinus walls (81 tumors), in the posterior pharyngeal wall (4 tumors) and in the postcricoid region (2 tumors). A total of 60 patients underwent surgery as the primary treatment option, and 27 were submitted to salvage pharyngolaryngectomy after a previous treatment with chemoradiotherapy or radiotherapy. The 5-year overall survival was of 25.9%, the 5-year disease-free survival was of 24.2%, and the disease-specific survival was of 29.5%. Conclusion The patients treated with pharyngolaryngectomy as the primary option revealed a better 5-year-disease free survival than the patients who underwent the salvage surgery (35.8% versus 11.7% respectively; p< 0.05). The histopathological criteria of capsular rupture of the lymph nodes (30.1% versus 19.8% respectively for the primary and salvage groups; p< 0.05) and vascular invasion (30.5% versus 22.5% respectively; p< 0.05) reduced the 5-year disease-free survival. Pharyngolaryngectomy as the primary intent revealed a lower local recurrence rate than the salvage surgery (40.6% versus 83.3% respectively; p< 0.05).

Cirugía transoral en hemangiomas de laringe e hipofaringe en adultos / Transoral surgery in laryngeal hemangiomas e hypopharynx in adults

Los hemangiomas son tumores benignos infrecuentes en la laringe. El tratamiento está indicado cuando el tumor produce síntomas (disnea, hemoptisis, odinofagia) y también cuando el riesgo de hemorragia severa por traumatismo es alto. Tres hemangiomas de laringe e hipofaringe fueron tratados con éxito por vía transoral con láser de C02 y radiofrecuencia. Todos los pacientes se alimentaron por vía oral a las 24/48 horas y ninguno tuvo traqueostomía. La tasa de resección completa de los hemangiomas tratados por vía transoral fue 100%. (AU)

Hemangiomas are a rare type of benign tumors of the larynx. The treatment is indicated when the tumor produces symptoms (dyspnea, hemoptysis, odynophagia) and also when the risk of severe bleeding from trauma is high. Three hemangiomas of the larynx and hypopharynx were successfully treated transorally with C02 laser and radiofrequency. All were orally fed at 24/48 hours, and none had a tracheostomy The complete resection rate of hemangiomas treated transorally was 100%. (AU)

Oncological results of surgical treatment versus organ-function preservation in larynx and hypopharynx câncer / Resultado oncológico de tratamento cirúrgico versus protocolo de preservação de órgão em câncer de laringe e hipofaringe

Summary Introduction: Since the beginning of the 1990s, non-surgical radiochemotherapy treatment has become popular with the prospect of maintaining oncological results and preserving the organ in patients with advanced squamous cell carcinoma of the larynx and hypopharynx. However, subsequent studies demonstrated increased recurrence and mortality after the non-surgical treatment became popular. Objective: To compare the oncological results of surgical and non-surgical treatments of patients with larynx and hypopharynx cancer and to evaluate the variables associated with disease recurrence. Method: This is a retrospective cohort study of 134 patients undergoing surgical (total or partial laryngectomy) or non-surgical (isolated radiotherapy, chemotherapy or induction chemotherapy followed by radiotherapy and chemotherapy) treatment, with 62 patients in the surgical group and 72 in the non-surgical group. Results: Disease-free survival rates were higher in the surgical group (81.7% vs. 62.2%; p=0.028), especially in III/IV stages (p=0.018), locally advanced tumors T3 and T4a (p=0.021) and N0/N1 cases (p=0.005). The presence of cervical lymph nodes, especially N2/N3, was considered a risk factor for disease recurrence in both groups (HR=11.82; 95CI 3.42-40.88; p<0.0001). Patients not undergoing surgical treatment were 3.8 times more likely to develop recurrence (HR=3.76; 95CI 1.27-11.14; p=0.039). Conclusion: Patients with larynx or hypopharynx cancer non-surgically treated had a poorer disease-free survival, especially in cases with locally advanced tumors (T3 and T4a) and in which the neck was only slightly affected (N0/N1).

Resumo Introdução: A partir de estudos do início dos anos 1990, popularizou-se o tratamento não cirúrgico com radioquimioterapia, com a perspectiva de manutenção do resultado oncológico e preservação do órgão em pacientes com carcinoma espinocelular avançado de laringe e hipofaringe. Entretanto, estudos posteriores demonstraram aumento da recorrência e da mortalidade com a difusão do tratamento não cirúrgico. Objetivo: Comparar o resultado oncológico dos tratamentos cirúrgico e não cirúrgico de pacientes com câncer de laringe e hipofaringe e avaliar as variáveis associadas à recidiva de doença. Método: Estudo de coorte retrospectiva de pacientes submetidos ao tratamento cirúrgico (laringectomia total ou parcial) e não cirúrgico (radioterapia isolada, radioterapia concomitante a quimioterapia ou quimioterapia de indução seguida de radioterapia e quimioterapia) de 134 pacientes, sendo 62 no grupo cirúrgico e 72 no não cirúrgico. Resultados: As taxas de sobrevivência livre de doença foram maiores no grupo cirúrgico (81,7% vs. 62,2%; p=0,028), principalmente em estádios III/IV (p=0,018), tumores localmente avançados T3 e T4a (p=0,021) e casos N0/N1 (p=0,005). A presença de linfonodos cervicais, principalmente N2/N3, foi considerada fator de risco para recidiva de doença nos dois grupos (HR=11,82; IC95% 3,42-40,88; p<0,0001). Pacientes não submetidos ao tratamento cirúrgico apresentaram 3,8 vezes mais chance de desenvolvimento de recidiva (HR=3,76; IC95% 1,27-11,14; p=0,017). Conclusão: Pacientes com câncer de laringe ou hipofaringe tratados de forma não cirúrgica tiveram menor sobrevivência livre de doença, especialmente nos tumores localmente avançados (T3 e T4a) e com pescoço pouco comprometido (N0/N1).

Thyroid gland invasion in advanced squamous cell carcinoma of the larynx and hypopharynx / Invasão da glândula tireoide no carcinoma espinocelular avançado de laringe e hipofaringe

Abstract Introduction: Squamous cell carcinoma of the larynx and hypopharynx has the potential to invade the thyroid gland. Despite this risk, the proposition of either partial or total thyroidectomy as part of the surgical treatment of all such cases remains controversial. Objectives: To evaluate the frequency of invasion of the thyroid gland in patients with advanced laryngeal or hypopharyngeal squamous cell carcinoma submitted to total laryngectomy or pharyngolaryngectomy and thyroidectomy; to determine whether clinic-pathological characteristics can predict glandular involvement. Methods: A retrospective case series with chart review, from January 1998 to July 2013, was undertaken in a tertiary care university medical center. An inception cohort of 83 patients with larynx/hypopharynx squamous cell carcinoma was considered. All patients had advanced stage disease (clinically T3-T4) and underwent total laryngectomy or total pharyngolaryngectomy in association with thyroidectomy. Adjuvant therapy was indicated when tumor or neck conditions required. Frequency of thyroid cartilage invasion was calculated; univariate and multivariate analysis of demographic, clinical and pathological characteristics associated with cartilage invasion were performed. Results: The overall frequency of invasion of the thyroid gland was 18.1%. Glandular involvement was associated with invasion of the following structures: anterior commissure (odds ratio = 5.13; 95% confidence interval 1.07-24.5), subglottis (odds ratio = 12.44; 95% confidence interval 1.55-100.00) and cricoid cartilage (odds ratio = 15.95; 95% confidence interval 4.23-60.11). Conclusions: Invasion of the thyroid gland is uncommon in the context of laryngopharyngeal squamous cell carcinoma. Clinical and pathological features such as invasion of the anterior commissure, subglottis and cricoid cartilage are more associated with glandular invasion.

Resumo Introdução O carcinoma espinocelular de laringe e hipofaringe tem potencial para invadir a glândula tireoide. Apesar desse risco, a proposição de tireoidectomia parcial ou total como parte do tratamento cirúrgico de todos esses casos permanece controversa. Objetivos Avaliar a frequência de invasão da glândula tireoide em pacientes com carcinoma espinocelular avançado de laringe ou hipofaringe submetidos a laringectomia total ou faringolaringectomia e tireoidectomia; determinar se características clínico‐patológicas podem prever o envolvimento glandular. Método Uma série de casos retrospectivos com revisão de prontuários, entre janeiro de 1998 e julho de 2013, foi feita em um centro médico universitário de cuidados terciários. Uma coorte inicial de 83 pacientes com carcinoma espinocelular de laringe/hipofaringe foi considerada. Todos os pacientes tinham doença em estágio avançado (clinicamente T3‐T4) e foram submetidos a laringectomia total ou faringolaringectomia em associação com tireoidectomia. Foi indicada terapia adjuvante quando o tumor ou as condições do pescoço exigiram. A frequência de invasão de cartilagem da tireoide foi calculada; análises univariada e multivariada das características demográficas, clínicas e patológicas associadas à invasão de cartilagem foram feitas. Resultados A frequência global de invasão da glândula tireoide foi de 18,1%. O envolvimento glandular foi associado à invasão das seguintes estruturas: comissura anterior (odds ratio = 5,13; intervalo de confiança 95%, 1,07‐24,5), subglote (odds ratio = 12,44; intervalo de confiança 95%, 1,55‐100,00) e cartilagem cricoide (odds ratio = 15,95; intervalo de confiança 95%, 4,23‐60,11). Conclusões A invasão da glândula tireoide é rara no contexto de carcinoma espinocelular laringofaríngeo. As características clínicas e patológicas, como a invasão da comissura anterior, subglote e cartilagem cricoide, estão mais associadas a invasão glandular.

Histologic correlation of VEGF and COX-2 expression with tumor size in squamous cell carcinoma of the larynx and hypopharynx.

The prognosis and survival of patients with laryngeal and hypopharyngeal squamous cell carcinoma (SCC) are related to the clinical staging. Tumor growth and metastasis are closely related to angiogenesis. Vascular endothelial growth factor (VEGF) and cyclooxygenase 2 (COX-2) are intimately related to the angiogenic process in which the blood supply required for neoplastic evolution is ensured. Considering the contributions of VEGF and COX-2 to the formation, growth, and progression of primary tumors, as well as their metastasis, it has been thought that the expression of these two factors might be related to the size and/or aggressiveness of laryngeal and hypopharyngeal cancer. To test that theory, we conducted a retrospective study to evaluate the expression of VEGF and COX-2 markers in archived specimens of SCC of the larynx and hypopharynx to correlate their expression with tumor size. These specimens had been obtained from 35 patients-31 men and 4 women, aged 37 to 75 years (mean: 57)-who had been treated for laryngeal or hypopharyngeal SCC at our tertiary care university hospital over a period of 15 years. Immunohistochemical analyses were performed with avidin-biotin-peroxidase staining for VEGF and COX-2 antibodies. The degree of VEGF and COX-2 expression was based on the German scale of immunoreactivity. Specimens were separated into groups based on the intensity of expression (none/low and moderate/strong) and tumor size (TNM categories T1/T2 and T3/T4). A total of 7 patients exhibited moderate or strong VEGF expression (3 from the T1/T2 group and 4 from the T3/T4 group), and 17 patients demonstrated moderate or strong COX-2 expression (8 from the T1/T2 group and 9 from the T3/T4 group). We found no statistically significant relationship between tumor size and either VEGF or COX-2 expression. Our study demonstrated that despite the intrinsic connection between and VEGF and COX-2, neither appears to be related to the size of the SCCs of the larynx or hypopharynx. Other factors must be involved in the pathogenesis and progression of this disease, and further studies are needed to identify them.